Membrane receptor molecules play a central role in many cellular processes including growth control, differentiation, and hormone responsiveness. Membrane immunoglobulin M (IgM) is the receptor for a development signal which stimulates a small B lymphocyte to differentiate into an IgM secreting plasma cell. The structure of the membrane IgM glycoprotein has recently been determined and compared with secreted IgM using B lymphocyte tumors from inbred mice. These two forms are identical except for their carboxytermini. The membrane form has a hydrophobic "tail" for membrane interaction and the secreted form a hydrophilic "tail" which allows it to form multimers and to be secreted. One gene encodes the constant region of mu; separate gene segments encode the alternative carboxytermini. It is thought that the two forms of mu are produced by alternative RNA splicing of a single primary transcript. We propose to study mouse tumor cells which synthesize both membrane (mIgM plus) and secreted IgM (sIgM plus). We will select mIgM minus SIgM plus mutant cells by treatment with anti-mu-antibody and complement. After cloning, the mIgM minus sIgM plus cells will be analyzed to determine their defect. Genetic and biochemical analysis of these mutants will allow us to determine the basic requirements for membrane-protein interactions, and for the alternative RNA processing of the mu transcript.